Immortalized human hepatocytes as a tool for the study of hepatocytic (de-)differentiation

Schippers, I.J.; Moshage, H.; Roelofsen, H.; Müller, M.; Heymans, H.S.A.; Ruiters, M.; Kuipers, F.

doi:10.1023/a:1007404028681

Cited by 110Drug Transport and Resistance MechanismsLiver physiology and pathologyHepatocellular Carcinoma Treatment and Prognosis

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Immortalized human hepatocytes as a tool for the study of hepatocytic (de-)differentiation

Schippers, I.J., Moshage, H., Roelofsen, H., Müller, M., Heymans, H.S.A., Ruiters, M., Kuipers, F.·1997·Cell Biology and Toxicology

DOI 10.1023/a:1007404028681

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Abstract

Primary human hepatocytes were immortalized by stable transfection with a recombinant plasmid containing the early region of simian virus (SV) 40. The cells were cultured in serum-free, hormonally defined medium during the immortalization procedure. Foci of dividing cells were seen after 3 months. Albumin- and fibrinogen-secreting cells were selected and cloned by limiting dilution to obtain homologous cell populations. The established IHH (immortalized human hepatocyte) cell lines were evaluated for their usefulness in studying the regulation of cell growth and of certain differentiated hepatocyte functions. IHH cells retain several differentiated features of normal hepatocytes. They display albumin secretion at a level comparable to cultured primary human hepatocytes (30 micrograms albumin/ml per day). A portion of the IHH cells are polarized, forming bile canaliculi-like vacuoles where exogeneous organic anions accumulate. The multidrug resistance (MDR) P-glycoprotein, known to be localized at the canalicular membrane, is also present in these vacuoles. The polarized features allowed the use of IHH cells for the study of localization of the newly characterized multidrug resistance protein MRP1. The homologues of MRP were found in hepatocytes, MRP1 and MRP2 (cMOAT), both functioning in ATP-dependent excretion of anionic conjugates. In differentiated hepatocytes, MRP1 expression is extremely low. In contrast, MRP1 is highly expressed in proliferating IHH cells, where it is l…

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Similar data were obtained using a non-cancerous human immortalized hepatic cell-line (IHH) used as another model of partially dedifferentiated hepatocytes.
“Similar data were obtained using a non‐cancerous human immortalized hepatic cell‐line (IHH) used as another model of partially dedifferentiated hepatocytes (Schippers et al, 1997; Fig EV4A–C).”
From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Schippers et al, 1997

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Willems M, Roskams T, Moshage H, Roels L, Desmet VJ, Yap SH. Immortalized human liver cell lines with phenotypical characteristics of hepatoblast and/or biliary epithelial cells: an in vitro model for the study of liver cell-specific func-tions. Transplantology (Madrid). 1994;5:151–9.

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Authors: Schippers, I. J., Moshage, H., Roelofsen, H., Müller, M., Heymans, H. S. A., Ruiters, M., & Kuipers, F.
Affiliations: University Medical Center Groningen (NL)
ORCID: Moshage, H.
Müller, M.
Kuipers, F.
Venue: Cell Biology and Toxicology
Publisher: Springer Science and Business Media LLC
Published: 1997-07
Volume: 13
Issue: 4-5
Pages: 375-386
ISSN: 0742-2091 (ISSN-L)
1573-6822
DOI: 10.1023/a:1007404028681
OpenAlex: W1503996899
Cited by: 110
References: 21
Citations by year: 2026: 3 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 6 · 2013: 3 · 2012: 5
FWCI: 0.60
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Cell Biology and Toxicology (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords: hepatocyte differentiation, hepatocyte dedifferentiation, SV40 early region, albumin secretion, fibrinogen secretion, P-glycoprotein, MRP2, organic anion transport, taurocholate uptake, triglyceride-rich lipoproteins, apolipoprotein B, apolipoprotein A-I, hepatocyte proliferation, hepatocyte culture
MeSH terms: MutS Homolog 3 Protein, Bile Acids and Salts, Blood Proteins, Cell Differentiation, Cell Line, Cell Survival, DNA-Binding Proteins, Enzyme-Linked Immunosorbent Assay, Humans, Liver, Male, Middle Aged, Plasmids, Simian virus 40, Transfection, Triglycerides, Cell Polarity, ATP Binding Cassette Transporter, Subfamily B, Member 1, ATP-Binding Cassette, Sub-Family C Proteins

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Immortalized human hepatocytes as a tool for the study of hepatocytic (de-)differentiation

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